Hydrolysis of Bone-Replacing Materials Based on Polylactic Acid and Containing Hydroxyapatite in an In Vitro Experiment.

We studied the features of hydrolytic degradation of polylactic acid (PLLA) implants depending on their structural filling with hydroxyapatite (HA). The resistance to in vitro hydrolysis was tested for the following samples: PLLA without HA (control; group 1), PLLA/HA 25 wt% (group 2), and PLLA/HA 50 wt% (group 3). Samples were incubated at 37°C. In the hydrolysate, lactate, calcium ions, and inorganic phosphate were determined. Additionally, the time of appearance of visual deformation and sample disintegration was recorded. PLLA degradation was higher in samples saturated with HA. The highest resistance to deformation was noted for samples without HA. Samples with a PLLA/HA 50 wt% demonstrated the maximum degradation of PLLA in combination with lower resistance to deformation and the highest bioavailability of calcium and phosphate. Group 2 samples are most promising for clinical use.

Solution blow spinning of PLLA/hydroxyapatite composite scaffolds for bone tissue engineering.

Composite poly-L-lactide acid-based scaffolds with hydroxyapatite (HAp) content up to 75 wt.% were fabricated via solution blow spinning. The influence of HAp concentration on structure, wettability, mechanical properties and chemical and phase composition of the produced materials was examined. It was found that with an increase of HAp content the average fiber diameter was increased, the uniaxial strength and relative elongation were reduced, while the phase composition and surface wettability did not change. The performance of the scaffolds during implantation in the parietal bone of a rat skull for a period from 15 to 90 days was studied. The materials have shown high ability to integrate with both soft and hard tissues. It was found that scaffolds with 25 wt.% HAp content significantly enhance osteogenesis during scarification (damage) of the periosteum. Overall, the fabricated scaffolds proved to be highly efficient for replacing bone defects in long tubular bones.

Bone Formation and Adaptive Morphology of the Anterior Tibial Muscle in 3-mm Daily Lengthening Using High-Fractional Automated Distraction and Osteosynthesis with the Ilizarov Apparatus Combined with Intramedullary Hydroxyapatite-Coated Wire.

PURPOSE: We studied osteogenesis and morphofunctional features of the anterior tibial muscle using 3-mm high-frequency automated lengthening with the Ilizarov apparatus alone and in combination with intramedullary nailing. MATERIAL AND METHODS: Tibia was lengthened with a round-the-clock automated distractor at a 3-mm daily rate for 10 days in 16 mongrel dogs. In group 1 (n = 8), a 1.8-mm intramedullary titanium wire coated with hydroxyapatite was introduced into the tibial canal followed by Ilizarov frame mounting and transverse osteotomy of the diaphysis. Distraction mode was 0.025 mm x 120 increments a day. In group 2 (n = 8), distraction mode was the same but nailing was not used. Bone formation and the anterior tibial muscle were studied at two time points: (1) upon distraction completion; (2) three months after the apparatus removal. Bone formation was studied radiographically. Muscle preparations were examined histologically and stereomicroscopically. RESULTS: There was a threefold reduction in the distraction time in both groups. Consolidation took 13.83±4.02 days in group 1 and 33.7±2.4 days in group 2. Muscle macropreparations of the experimental limb in group 1 at study time points did not show significant differences from intact tissues. Muscle histostructure in both groups was characterized by activation of angiogenesis and myohistogenesis, but the volumetric density of microvessels in the lengthening phase was three times higher in group 1. CONCLUSION: Combined technology significantly reduces the total lengthening procedure and does not compromise limb functions. Intramedullary HA-coated wires promote faster bone formation. The muscle was able to exhibit structural adaptation and plasticity of a restitution type.

Flexible intramedullary nails for limb lengthening: a comprehensive comparative study of three nails types.

This study aims to investigate the comparative study of calcium phosphate coatings for flexible intramedullary nails (FINs) used to lengthen long tubular bones. The presence of a calcium phosphate coating deposited by micro-arc oxidation (MAO) or a composite coating based on a co-polymer of vinylidene fluoride with tetrafluoroethylene (VDF-TeFE) and hydroxyapatite (HA) on the surface of the FIN significantly enhanced the regeneration of bone in the area of osteotomy during limb lengthening by combined osteosynthesis. The investigation of the physico-chemical properties of the FIN coated with calcium phosphate via MAO demonstrated that the improved bone tissue formation resulted from favourable conditions for adhesion, proliferation and differentiation of multipotent stem cells into osteoblasts on the coating surface. The composite coatings only stimulated the formation of bone tissue in vivo, primarily because of the piezoelectric properties of the VDF-TeFE co-polymer.

Osteoinductive composite coatings for flexible intramedullary nails.

This work presents composite coatings based on a copolymer of vinylidene fluoride with tetrafluoroethylene (VDF-TeFE) and hydroxyapatite (HA) for flexible intramedullary nails (FIN). The effect of the proportion of VDF-TeFE (100-25% wt.) on physicochemical and biological properties of the composite coatings was investigated. It was shown that a decrease of VDF-TeFE in the coating hinders its crystallization in ß and γ forms which have piezoelectric properties. The decrease also reduces an adhesive strength to 9.9±2.4MPa and a relative elongation to 5.9±1.2%, but results in increased osteogenesis. It was demonstrated that the composite coatings with 35% VDF-TeFE has the required combination of physicochemical properties and osteogenic activity. Comparative studies of composite coatings (35% VDF-TeFE) and calcium phosphate coatings produced using micro-arc oxidation, demonstrated comparable results for strength of bonding of these FINs with trabecular bones (~530MPa). It was hypothesized that the high osteoinductive properties of the composite coatings are due to their piezoelectric properties.

[Blood Flow and Regional Blood Flow Rate in the Middle Cerebral Artery during Surgical Leg Lengthening in Patients with Congenital and Acquired Limb Shortening].

This is a comparative study of changes in blood flow rate in the popliteal artery, the arteries of bone regenerate and cerebral arteries in 45 patients with congenital and acquired diseases of the limbs at different stages of surgical lengthening of 3-15 cm shortened shin by Ilizarov method. We observed an increase in regional blood flow rate in all patients during the periods of distraction and fixation. A 25% increase in blood flow rate in the middle cerebral artery on the contralateral side was found only in patients of the first adult age with acquired limb shortening. Basing on the analysis of the reaction of cerebral arteries during a functional test with additional muscle work, we suggested that the absence of reaction in congenital diseases is caused by relative excess of somatic afferentation which results from morphological and functional immaturity of brain regulatory systems.

Bone healing by using Ilizarov external fixation combined with flexible intramedullary nailing versus Ilizarov external fixation alone in the repair of tibial shaft fractures: experimental study.

PURPOSE: Our research was aimed at studying the radiographic and histological outcomes of using flexible intramedullary nailing (FIN) combined with Ilizarov external fixation (IEF) versus Ilizarov external fixation alone on a canine model of an open tibial shaft fracture. MATERIALS AND METHODS: Transverse diaphyseal tibial fractures were modelled in twenty dogs. Fractures in the dogs of group 1 (n = 10) were stabilized with the Ilizarov apparatus while it was combined with FIN in group 2 (n = 10). RESULTS: On day 14, a bone tissue envelope started developing round the FIN wires. Histologically, we revealed only endosteal bone union in group 1 while in group 2 the radiographs revealed complete bone union on day 28. At the same time-point, the areas of cancellous and mature lamellar bone tissues were observed in the intermediary area in group 2. The periosteal layers were formed of the trabeculae net of lamellar structure and united the bone fragments. The frame was removed at 30 days after the fracture in group 2 and after 45 days in group 1 according to bone regeneration. CONCLUSION: The combination of the Ilizarov apparatus and FIN accelerates bone repair and augments stabilization of tibial shaft fractures as compared with the use of the Ilizarov fixation alone.

Experimental study of progressive tibial lengthening in dogs using the Ilizarov technique. Comparison with and without associated intramedullary K-wires.

UNLABELLED: A delay in the union of bone regenerate in surgical lengthening procedures and the healing index (HI) are major factors in the quality of the results in progressive bone lengthening. Early removal of the external fixator (EF) is associated with a low rate of postoperative complications, including pin track infection, and with better muscle and joint function recovery. Addition of intramedullary wires (IMWs) to the EF led to a 9-49% decrease in the HI depending on the clinical series. We hypothesized that IMWs may accelerate the ossification process of bone regenerate and tested it in this experimental study. METHODS: Progressive tibial lengthening of 28 mm was obtained in 12 dogs operated with the classical Ilizarov technique (group I) and in 12 dogs operated with the same technique and addition of two IMWs 1.5 mm in diameter (group II). The following criteria were assessed: HI, X-ray measurements, and histological aspect of the bone regenerate and postoperative complications. RESULTS: The mean HI was 32.3% lower in group II than in group I. The radiological bone union criteria were observed on day 15 of the fixation period in group II versus day 30 in group I. Histology showed that maturation occurred earlier and bone cortices were thicker in group II than group I. Intramedullary ossification was present along the IMW in group II, whereas it was absent in group I. No clinical complications were observed in either group. DISCUSSION: The presence of the IMWs clearly contributes to stimulation of the ossification processes of the bone regenerate and to acceleration of bone union. IMWs allowed an earlier removal of the external fixator for a 32% time reduction compared to cases without IMWs. In addition, new intramedullary bone formation and presence of IMWs are expected to increase the mechanical resistance of the bone regenerate. CONCLUSION: Improvement of quantitative and qualitative criteria of bone regenerate in progressive bone lengthening with an EF combined with IMWs was demonstrated in this experimental study. SIGNIFICANCE: Favorable results encourage the authors to continue using IMWs in addition to the EF in patients treated with long-bone progressive lengthening. LEVEL OF EVIDENCE: II.

[Morphological characteristics of reparative osteogenesis under the conditions of transosseous osteosynthesis and intramedullary introduction of hydroxyapatite-coated wires].

In the experiments performed on 16 dogs, an open comminuted tibial fracture was modeled, then wires with hydroxyapatite coating were inserted intramedullary, and osteosynthesis was performed using the Ilizarov fixator. Bone regenerates were studied 14-360 days after the surgery using the methods of light microscopy, scanning electron microscopy, and X-ray electron probe microanalysis. It was found that a zone of active reparative osteo- and angiogenesis was formed around the wires, as well as a bone sheath with the properties of osteogenesis conductor and inductor. Fracture consolidation occured early according to the primary type without cartilaginous and connective tissue formation in bone adhesion.

[Fracture healing under intramedullary insertion of wires with hydroxyapatite coating].

AIM: To study morphological features of the bone formation process in consolidation of fractures of long tubular bones in conditions of intramedullary wires insertion with bioactive calcium-phosphate coating of hydroxyapatite. MATERIALS AND METHODS: In experimental study in dogs was simulated open comminuted tibia fracture and performed intramedullary insertion of wires with hydroxyapatite coating. Using light and electron microscopy, using X-ray electron microprobe microanalyses were studied bone regenerates in 14-360 days after surgery. RESULTS: It was found that around wires there is a formation of an area of active reparative bone formation and angiogenesis, bone shaped case with the properties of the conductor and inducer of osteogenesis. Fracture consolidation is carried out in the early stages of the primary type without formation of cartilage and connective tissue in the bone adhesion. CONCLUSION: Study results testify that intramedullary wires with hydroxyapatite coating positively influence on the process and intensity of reparative bone formation in fracture healing.

[Nonreconstructive revascularizing operations in limb ischaemia].

Presented herein are the findings of experimental studies substantiating interrelationship between osteogenesis and blood circulation, as well as effects of surgical interventions based on excitation of reparative regeneration of the bone and aimed at improvement of blood circulation in the extremities. Reflected also are the main indications for the use of each operative intervention concerned. Based on the clinical findings obtained by follow up of 1,477 patients operated on for limb ischaemia secondary to obliterating arterial lesions efficacy of the methods of treatment devised is demonstrated.

[Dynamics of acoustic properties of skin integument and hydroxyproline content during surgical treatment of congenital limb malformation].

The aim of the work was to examine mechanical and acoustic properties of the skin and collagen metabolism in patients with congenital and developmental malformation (CDM) of extremities. Acoustic tests were performed in 39 patients with forearm CDM and in 30 with leg CDM aged 4-18 years using an ASA-4 apparatus (Russia and Yugoslavia). Mean radial and ulnar lengthening was 6.4 +/- 1.0 (5.5-8) cm, tibial and fibular lengthening 5.0 +/- 1.2 (3-8) cm, and femoral lengthening 6-12 cm. Longitudinalvelocity of sound 1 and 2 months after distraction was 42.3% and 62.9% respectively higher than the preoperative value (p < 0.05). A similar increase (36.8 and 58.4% respectively) was recorded with the ASA-4 sensor in the transverse position. Acoustic inhomogeneity in the thigh skin also increased during distraction. Maximum free to protein-bound hydroxyproline ratio in blood was measured in the end of distraction (0.58 +/- 0.04) and in the beginning of fixation (0.6 +/- 0.01). Its subsequent decrease reflected structural and metabolic changes related to proliferative and biosynthetic processes in the skin, fibrillogenesis, and altered homogeneity patterns.

[Elastic stable intramedullary nailing in Ilizarov bone lengthening]. / Embrochage centro-médullaire dans les allongements osseux selon Ilizarov.

PURPOSE OF THE STUDY: Bone lengthening with the Ilizarov technique gives good results but certain disadvantages are common: possible axial deviation during lengthening, long time to bone union, risk of fracture after removal of the external fixator. Associating the Ilizarov technique with elastic stable intramedullary nailing (ESIN) commonly used in traumatology has to be evaluated. We conducted an experimental study and report results of the first clinical application. MATERIAL AND METHODS: Eleven lengthenings of the tibia were conducted in dogs aged 1 to 4 years using an Ilizarov external fixator associated with ESIN. Lengthening started on day 1 and continued for 28 days. X-rays were obtained every week during lengthening, then at 15 and 30 days during the fixation period and 30 days after removal of the fixator. In two cases, arteriography was performed. In a pilot clinical trial, fourteen patients (8 males, 6 females) were treated with this method (1 humerus, 1 forearm, 7 femurs, 5 tibias). Mean patient age was 14 years. RESULTS: In the experimental study, the x-rays showed rapid ossification of the regenerate which led to increased tibia length in 7 cases from 1.25 to 2 mm/day. Total bone union was observed in four dogs during the lengthening period. At day 15 of the fixation period, all tibia had fused with a good quality cortical bone and healing of the growth part of the regenerate. In three dogs, the external fixator was removed at day 15 of fixation and weight-bearing was total with the ESIN in place. No axial deviation and no skin problems were observed. The medullary artery was seen on the two arteriograms. In the clinical trial, bone union of the regenerate appeared earlier than in the Ilizarov series. The regenerate always displayed good density on the x-rays, proving intense bone activity. In three patients, the lengthening rate was increased to avoid premature bone fusion. The endosteal bone regenerate was obvious. Mean healing index was 18.6 days/cm (SD=6.2). Weight-bearing was allowed at six weeks. The desired correction was achieved in all patients and no complications were related to ESIN. DISCUSSION: Bone lengthening may be obtained with an intramedullary locking nail which avoids the use of an external fixator but also destroys the endomedullary circulation. Our experimental and clinical study shows that use of an ESIN does not inhibit the endosteal regenerate and seems to improve new bone formation. In many patients, the lengthening rate had to be increased to avoid premature bone fusion. When used in optimal conditions, ESIN can stimulate new endosteal and periosteal bone formation. In addition, ESIN increases shaft stability avoiding the risk of axial deviation. ESIN plays an additional role of stabilization after early removal of the external fixation.

[Dynamics of echomorphometric human crural skin characteristics during dosed stretching]. / Dinamika ékhomorfometricheskikh pokazatelei kozhi goleni cheloveka v usloviiakh dozirovannogo rastiazheniia.

The dynamics of echo-morphometric parameters of crural skin was studied in patients with congenital shortening of lower extremity in the process of its operative elongation. It is demonstrated that dosed stretch results in increased skin thickness. After the completion of distraction, the skin thickness exceed preoperation levels by 48.7% (in patients aged 5-8 years), 20.9% (in patients aged 10-14 years) and 26.7% (in adults). Skin acoustic density after distraction termination reached the preoperation level in children and adolescents, while it was increased in adults.

[Biochemical and anatomic changes in the muscles after leg bone lengthening by the Ilizarov method]. / Biokhimicheskie i anatomicheskie izmeneniia v myshtsakh pri udlinenii nizhnikh konechnostei po Ilizarovu.

In process of crus lengthening, following the method, given by Ilizarov G. A., with 22 adult patients have been studied the peculiarities of metabolic processes of muscle tissue of the lengthened segment as well as the muscle tissue structural changes. As the tests were used; determination of lactate dehydrogenase content and its isoenzymatic spectrum in the blood serum, the residual products of lactic and pyruvic acids glycolysis, relating to the higher indications of the internal medium of an organism; carboxylase activity detection. Energy provision of an organism was estimated according to the ATP content; anatomical state of muscles of the lengthened extremity segment and muscle tissue structure were estimated by means of contrast myography. Dynamics of biochemical indexes suggests that the sparing character of an operation, patient mobility from the first days, preservation of locomotive and supporting function contribute to prevention of metabolic disease and ensure earlier transformation of catabolic reaction to anabolic one. Carboxylase and lactate-dehydrogenase activity increase indicates the biochemical adaptation of an organism. Metabolic changes well correlate with the detected structural changes in the lengthened crus muscles.

[Significance of contrast radiography in the assessment of the state of the muscles and differential diagnosis of extensor contractures of the knee joint]. / Znachenie kontrastnoi rentgenografii v otsenke sostoianiia myshts i differentsial'noi diagnostiki razgibatel'nykh kontraktur kolennogo sustava.

On the basis of analysis of the roentgen contrast examination of femoral muscles of the patients with extension contractures of knee joint, roentgen systematics of the muscle changes at given pathology is presented and the criteria of differential diagnosis of contractures of different types are proposed. 55 patients (125 examinations) with extension contractures of knee joint (arthrogenic, immobilizing, due to myofascio-tenodesis) of different etiology were subjected to roentgen contrast myography. As a consequence, this offered a means of objective evaluation of the muscle state and enabled one to discover the changes of muscles, specific for contractures in general as well as for each type in particular. The table of roentgenologic signs has been compiled which permits to make differential diagnosis, determine the tactics of treatment, select the type of surgical intervention on the basis of the muscle condition.

[Clinical and biochemical indicators in patients undergoing limb lengthening using Ilizarov's method]. / Kliniko-biokhimicheskie pokazateli u bol'nykh pri udlinenii konechnosti po Ilizarovu.

The authors report that in 33 patients who underwent stretching of the extremity by the method of dosed distraction after G. A. Ilizarov following corticotomy there were no significant changes in a number of biochemical values (serum concentrations of general protein, albumin, urea, uric acid, glucose, cholesterol, triglycerides, magnesium, chlorides). The level of other values (alkaline phosphatase and lactate dehydrogenase enzymes, etc.) increased and sometimes exceeded the physiological limits of its age group, but did not exceed the normal limits in the population as a whole. A reliable change in the values was observed with their level being higher during the period of natural growth because of intensification of anabolic processes and growth of the mass of organs and tissues or increase in their function. A rise in serum concentrations of calcium, phosphate and hydroxyproline with the urine demonstrates in combination with the data of biphoton densimetry of the skeleton and distraction regenerate that at the same time with improved absorption of electrolytes in the intestines during distraction there was an activation of mobilization of the minerals from the intact skeleton. A problem of adequate consumption of mineral substances with the food is put forward.